The aim of the Embryonic Stem (ES) Cell Engineering facility is to accelerate research programs that depend on the development of genetically altered mouse models (knock-outs, knock-ins, and inducible knock-outs) that require ES cell manipulation. Successful ES cell engineering is a major hurdle for the realization of research goals for many NINDS investigators at JHU SOM (see below), and is currently performed by individual laboratories with varying degrees of success. The ES Cell Engineering Core will implement cutting-edge approaches for ES cell manipulation to assure that investigators use the most efficient strategies to generate animal models for NINDS supported research. These strategies will include generation of ES cells from existing mouse mutant lines for subsequent gene targeting and chimeric embryo production, and multi-hit transgenic targeting protocols that use novel recombination approaches for controlled site-directed mutagenesis. By establishing ES cell engineering as a core resource we will standardize protocols from the most successful laboratories, markedly increase the efficiency of model generation, and speed the pace of NINDS-supported research at JHU SOM. There is currently no core facility at JHU SOM that can perform ES cell engineering. The ES Cell Engineering Core will work in synergy with the current Transgenic Animal facility at JHU SOM, which provides complementary services such as injection of ES cells into blastocysts and animal husbandry necessary to achieve high chimera mice. There will be no overlap in the services provided by the ES Cell Engineering Core and the Transgenic Animal facility.